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The diagnosis of myelodysplastic syndromes (MDS) is based on morphological changes in the blood and bone marrow. The parameters NEUT-X and NEUT-Y of the Sysmex XE-2100 analyzer could help detect neutrophil dysplasia. A control group of 50 patients, along with 50 postpartum patients, 50 anemias, 50 leukopenias, 50 patients with microscopically visible hypergranulated neutrophils and 50 MDS patients were assessed. The NEUT-X and NEUT-Y values (mean +/- SD) for the control group were 1346 +/- 28.2 and 420 +/- 19.3, respectively, with the anemia and leukopenia groups giving similar values. The postpartum and hypergranulated neutrophils groups presented higher values (P < 0.05), whereas the values in the MDS group were 1286 +/- 72.8 and 385 +/- 50.9 (P < 0.05), respectively. There were no differences between the morphological MDS types. The NEUT-X and NEUT-Y values in MDS patients with optical hypogranulation were significantly lower than for MDS patients without optical hypogranulation. NEUT-X and NEUT-Y values lower than 1298 and 398, respectively, would have a specificity for detecting MDS of 94% and 91% and would detect 60% and 56% of cases, respectively, whereas they would detect 75% and 74%, respectively, of MDS cases with optical hypogranulation. NEUT-X and NEUT-Y parameters can be used to detect neutrophil dysplasia arising from MDS and chronic myelomonocytic leukemia.

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OBJECTIVE: To study the variability and suitability of antibiotic prescription in primary care in the Basque Country. DESIGN: Prospective, descriptive study. SETTING: Basque Country health care centres both within and not in the reformed network. MEASUREMENTS AND MAIN RESULTS: 3182 infections from consultations for infectious disease were studied through sampling stratified by health area during February, March and April 1998. The appropriateness of antibiotics (ATB) prescription was compared with some standards after an extensive bibliographic review. 68.6% of consultations were infections not needing ATB (infections of respiratory airways, acute bronchitis, flu and gastro-enteritis). ATB were used in 28.5% of these cases (CI: 26.6-30.5), especially in acute bronchitis (90.7%) (CI: 87.3-93.4). Unnecessary prescription supposes 39.7% of total antibiotic prescription (CI: 37.2-42.1%), which means unnecessary annual expenditure of 1155 million pesetas. In 31.4% of the infections that require ATB treatment, in 23.7% inappropriate treatment was chosen (CI: 21-26.7%). Overall appropriateness of treatment was 72.2% (CI: 70.6-73.8). Working in the reformed system was linked to better prescription in all cases. Paediatricians prescribed better in the case of infections not susceptible to ATB treatment. CONCLUSIONS: ATB prescription is not consistent with the available scientific evidence. Incorrect treatments occur especially in benign and self-limiting processes. A local policy of ATB use that includes multi-disciplinary collaboration and effective ongoing training is necessary.

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Objetivo. Estudiar la variabilidad e idoneidad de la prescripción antibiótica en atención primaria en la Comunidad Autónoma Vasca (CAV).Diseño. Estudio descriptivo, prospectivo. Emplazamiento. Centros de atención primaria de la red reformada y no reformada de la CAV. Mediciones y resultados principales. Se estudiaron 3.182 infecciones obtenidas de consultas sobre enfermedad infecciosa mediante muestreo estratificado por área sanitaria durante febrero, marzo y abril de 1998. La idoneidad de la prescripción de antibióticos (ATB) se comparó con unos patrones elaborados tras una extensa revisión bibliográfica. Un 68,6 por ciento de las consultas son infecciones que no requieren ATB (catarro de vías altas [IRA], bronquitis aguda, gripe y gastroenteritis). Se utilizan ATB en un 28,5 por ciento de estos casos (IC, 26,6-30,5). Destaca la bronquitis aguda, con un 90,7 por ciento (IC, 87,3-93,4). La prescripción innecesaria supone un 39,7 por ciento de la prescripción total antibiótica (IC, 37,2-42,1 por ciento), suponiendo un gasto anual innecesario de 1.155 millones de pesetas. En el 31,4 por ciento de las infecciones que requieren tratamiento con ATB, se opta por uno no adecuado en un 23,7 por ciento (IC, 21-26,7 por ciento). En total, la idoneidad del tratamiento global fue del 72,2 por ciento (IC, 70,6-73,8). El hecho de trabajar en la red reformada se asoció a una mejor prescripción en todos los casos. Los pediatras prescriben mejor en el caso de las infecciones no susceptibles de tratamiento con ATB. Conclusiones. La prescripción de ATB no se realiza conforme a la evidencia científica disponible. Los tratamientos incorrectos tienen lugar sobre todo en procesos benignos y autolimitados. Es necesaria una política local de uso de ATB que incluya colaboración multidisciplinaria y formación continuada efectiva (AU)

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We have examined the interaction of the human immunodeficiency virustype 1 fusion peptide (23 amino acid residues) and of a Trp-containing analog with vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol (molar ratio, 1:1:1). Both the native and the Trp-substituted peptides bound the vesicles to the same extent and induced intervesicular lipid mixing with comparable efficiency. Infrared reflection-absorption spectroscopy data are compatible with the adoption by the peptide of a main beta-sheet structure in a cospread lipid/peptide monolayer. Cryo-transmission electron microscopy observations of peptide-treated vesicles reveal the existence of a peculiar morphology consisting of membrane tubular elongations protruding from single vesicles. Tryptophan fluorescence quenching by brominated phospholipids and by water-soluble acrylamide further indicated that the peptide penetrated into the acyl chain region closer to the interface rather than into the bilayer core. We conclude that the differential partition and shallow penetration of the fusion peptide into the outer monolayer of a surface-constrained bilayer may account for the detected morphological effects. Such single monolayer-restricted interaction and its structural consequences are compatible with specific predictions of current theories on viral fusion.

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We have identified a region within the ectodomain of the fusogenic human immunodeficiency virus type 1 (HIV-1) gp41, different from the fusion peptide, that interacts strongly with membranes. This conserved sequence, which immediately precedes the transmembrane anchor, is not highly hydrophobic according to the Kyte-Doolittle hydropathy prediction algorithm, yet it shows a high tendency to partition into the membrane interface, as revealed by the Wimley-White interfacial hydrophobicity scale. We have investigated here the membrane effects induced by NH(2)-DKWASLWNWFNITNWLWYIK-CONH(2) (HIV(c)), the membrane interface-partitioning region at the C terminus of the gp41 ectodomain, in comparison to those caused by NH(2)-AVGIGALFLGFLGAAGSTMGARS-CONH(2) (HIV(n)), the fusion peptide at the N terminus of the subunit. Both HIV(c) and HIV(n) were seen to induce membrane fusion and permeabilization, although lower doses of HIV(c) were required for comparable effects to be detected. Experiments in which equimolar mixtures of HIV(c) and HIV(n) were used indicated that both peptides may act in a cooperative way. Peptide-membrane and peptide-peptide interactions underlying those effects were further confirmed by analyzing the changes in fluorescence of peptide Trp residues. Replacement of the first three Trp residues by Ala, known to render a defective gp41 phenotype unable to mediate both cell-cell fusion and virus entry, also abrogated the HIV(c) ability to induce membrane fusion or form complexes with HIV(n) but not its ability to associate with vesicles. Hydropathy analysis indicated that the presence of two membrane-partitioning stretches separated by a collapsible intervening sequence is a common structural motif among other viral envelope proteins. Moreover, sequences with membrane surface-residing residues preceding the transmembrane anchor appeared to be a common feature in viral fusion proteins of several virus families. According to our experimental results, such a feature might be related to their fusogenic function.

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A monoclonal IgM antibody that reacts with cholesterol was able to aggregate small and large unilamellar lipid vesicles. Vesicles aggregated by the antibody could be dispersed by trypsin digestion. Inclusion of unsaturated phosphatidylethanolamine in the vesicle formulation lowered the relative amount of cholesterol necessary for aggregation, and prevented disaggregation by trypsin treatment. Fluorimetric assays indicated that membrane mixing occurred in aggregates resistant to trypsinization, but the vesicles did not mix or leak their aqueous contents. Analysis of the kinetics of lipid-mixing showed an increase in the aggregation and fusion rate constants with increasing antibody concentrations, indicating that the antibody reaction promotes both processes. An apparent inactivation process whose rate increased with antibody dose has been considered. We conclude that the simultaneous binding of antibodies to more than one vesicle at densities that allow the contact of membrane surfaces, induces first aggregation followed by hemifusion, and with excess of antibody also results in inactivation of the latter process.

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